Several nmr experiments provide data which depend upon internuclear distances and details of molecular motion. These data include spin-lattice relaxation rates, spin-spin relaxation rates and perturbation of signal intensities by nuclear Overhauser effects. A careful analysis of such information can provide useful insights into protein structural features in solution and possibly will be applicable in studies of proteins on membrane surfaces. A number of technical and interpretational impediments to the application of these experiments to protein systems can be overcome by the introduction of a small number of fluorine atoms into the protein. This can be accomplished by covalent modification of amino acid residues or by biosynthetic incorporation of fluorine-containing amino acids. Moreover, small molecule binding sites on proteins can be examined by the same approaches when fluorine nuclei are placed on the interacting small molecule. In favorable circumstances the experiments indicated should (1) identify the amino acid residues near the fluorine nuclei, (2) provide some indication of the distances between these amino acids and the fluorines, and (3) generate estimate of the time scales for molecular motion near the fluorine atoms. With small molecule-protein complexes the rate of dissociation of the complex can also be determined by these methods. We propose to explore the use of fluorine nmr to elucidate protein structures from both experimental and theoretical directions and to develop procedures to simplify the application of the methodology so developed to the study of proteins involved in diseased states.